Gastric cancer is one of the leading causes of cancer-related deaths in the world. Despite major research and clinical efforts, the results for th treatment of gastric cancer in general have been poor and thus newer and effective therapies are necessary to combat this disease. With reports indicating that substantial amount of DA is produced in normal stomach tissues and DA mediates cytoprotection of gastric epithelial cells by acting through its receptors present in these cells, we therefore postulated that this non-neuronal dopaminergic system in the stomach might also play an important role in gastric tumorigenesis. Thus Aim 1 will investigate the role of non-neuronal stomach dopaminergic system in gastric tumorigenesis, Aim 2 will elucidate the signaling pathway through which dopamine D5 receptors regulate reactive oxygen species in stomach and Aim 3 will determine the therapeutic efficacies of DA D5 receptor agonists in gastric tumorigenesis. The knowledge generated from this study will help to develop newer and effective therapies for this disease, which, as of yet, has no significant treatment.